Case Study Conclusion: Defending Your Defenses
This woman is participating in a bike ride to raise funds for leukemia and lymphoma research. Leukemia and lymphoma are blood cancers. About every three minutes, one person in the U.S. is diagnosed with blood cancer. Lymphoma is the most common type of blood cancer. As a lymphoma patient, Wei, who you learned about in the beginning of this chapter, may eventually benefit from research funded by a bike ride like this one.
What type of blood cell is affected in lymphoma? As the name implies, lymphoma is a cancer that affects lymphocytes, which are a type of white blood cell. As you have learned in this chapter, there are different types of lymphocytes, including the B and T cells of the adaptive immune system. Different types of lymphoma affect different types of lymphocytes in different ways. It is important to correctly identify the type of lymphoma so that patients can be treated appropriately.
You may recall that one of Wei’s symptoms was a swollen lymph node, and he was diagnosed with lymphoma after a biopsy of that lymph node. Swollen lymph nodes are a common symptom of lymphoma. As you have learned, lymph nodes are distributed throughout the body along lymphatic vessels as part of the lymphatic system. The lymph nodes filter lymph and store lymphocytes and therefore play an important role in fighting infections. Because of this, they will often swell in response to an infection. In Wei’s case, the swelling and other symptoms did not improve after several weeks and a course of antibiotics, which caused Dr. Bouazizi to suspect lymphoma instead. The biopsy showed that Wei did indeed have cancerous lymphocytes in his lymph nodes.
But which type of lymphocytes were affected? Lymphoma most commonly affects B or T lymphocytes. The two major types of lymphoma are called Hodgkin (HL) or non-Hodgkin lymphoma (NHL). NHL is more common than HL. There are more than 70,000 cases of NHL diagnosed in the U.S. each year, compared to about 8,000 for HL. While HL is one distinct type of lymphoma, NHL has about 60 different subtypes, depending on which specific cells are affected and how.
Wei was diagnosed with a type of NHL called diffuse large B-cell lymphoma (DLBCL) — the most common type of NHL. This type of lymphoma affects B cells and causes them to appear large under the microscope. In addition to Wei’s symptoms of fatigue, swollen lymph nodes, loss of appetite, and weight loss, common symptoms of this type of lymphoma include fever and night sweats. It is an aggressive and fast-growing type of lymphoma that is fatal if not treated. But the good news is that with early detection and proper treatment, about 70 percent of patients with DLBCL can be cured.
How do physicians determine the specific type of lymphoma? Tissue obtained from a biopsy can be examined under a microscope to observe physical changes such as abnormal cell size or shape that are characteristic of a particular subtype of lymphoma. Additionally, tests can be performed on the tissue to determine which cell-surface antigens are present. Recall that antigens are molecules that bind to specific antibodies. Antibodies can be produced in the laboratory and labeled with compounds that can be identified by their color under a microscope. When these antibodies are applied to a tissue sample, this color will appear wherever the antigen is present, because it binds to the antibody. For example, this technique was used in the photomicrograph below to identify the presence of a cell-surface antigen (shown as reddish-brown) in a sample of skin cells. This technique, called immunohistochemistry, is also commonly used to identify antigens in tissue samples from lymphoma patients.
Why would identifying cell-surface antigens be important in diagnosing and treating lymphoma? As you have learned, the immune system uses antigens present on the surface of cells or pathogens to distinguish between self and non-self and to launch adaptive immune responses. Cells that become cancerous often change their cell-surface antigens, and this is one way that the immune system can identify and destroy them. Also, different cell types in the body can sometimes be identified by the presence of specific cell-surface antigens. Knowing the types of cell-surface antigens present in a tissue sample can help physicians identify which cells are cancerous, and possibly the specific subtype of cancer. Knowing this information can be helpful in choosing more tailored and effective treatments.
In fact, one treatment for NHL is the use of medications made from antibodies that bind to cell-surface antigens present on cells affected by the specific subtype of NHL. This is called immunotherapy. These drugs can directly bind to and kill the cancerous cells. For patients with DLBCL such as Wei, immunotherapy is often used in conjunction with chemotherapy and radiation as a course of treatment. Although Wei has a difficult road ahead, he and his medical team are optimistic that he may be able to be cured, given the high success rate when DLBCL is caught and treated early. More research into how the immune system functions may lead to even better treatments for lymphoma, and other types of cancers, in the future.
In this chapter, you learned about the immune system. Specifically, you learned that:
- Any agent that can cause disease is called a pathogen. Most human pathogens are microorganisms such as bacteria and viruses. The immune system is the body system that defends the human host from pathogens and cancerous cells.
- The innate immune system is a subset of the immune system that provides very quick but non-specific responses to pathogens. It includes multiple types of barriers to pathogens, leukocytes that phagocytize pathogens, and several other general responses.
- The adaptive immune system is a subset of the immune system that provides specific responses tailored to particular pathogens. It takes longer to put into effect, but it may lead to immunity to the pathogens.
- Both innate and adaptive immune responses depend on the ability of the immune system to distinguish between self and non-self molecules. Most body cells have major histocompatibility complex (MHC) proteins that identify them as self. Pathogens, infected cells, and tumor cells have non-self proteins called antigens that the immune system recognizes as foreign.
- Antigens are proteins that bind to specific receptors on immune system cells and elicit an adaptive immune response. Some immune cells (B cells) respond to foreign antigens by producing antibodies that bind with antigens and target pathogens for destruction.
- An important role of the immune system is tumor surveillance. Killer T cells of the adaptive immune system find and destroy tumor cells, which they can identify from their abnormal antigens.
- The neuroimmune system that protects the central nervous system is thought to be distinct from the peripheral immune system that protects the rest of the human body. The blood-brain and blood-spinal cord barriers are one type of protection of the neuroimmune system. Glial cells also play role in this system, for example, by carrying out phagocytosis.
- The lymphatic system is a human organ system that is a vital part of the adaptive immune system. It consists of several organs and a system of vessels that transport or filter the fluid called lymph. The main immune function of the lymphatic system is to produce, mature, harbor, and circulate white blood cells called lymphocytes, which are the main cells in the adaptive immune system and are circulated in the lymph.
- The return of lymph to the bloodstream is one of the functions of the lymphatic system. Lymph flows from tissue spaces, where it leaks out of blood vessels, to major veins in the upper chest, where it is returned to the cardiovascular system. Lymph is similar in composition to blood plasma. Its main cellular components are lymphocytes.
- Lymphatic vessels called lacteals are found in villi that line the small intestine. Lacteals absorb fatty acids from the digestion of lipids in the digestive system. The fatty acids are then transported through the network of lymphatic vessels to the bloodstream. Although it plays a role in digestion, the primary function of the lymphatic system is host defense.
- Lymphocytes, which include B cells and T cells, are the subset of white blood cells that are involved in adaptive immune responses. They may create a lasting memory of and immunity to specific pathogens.
- All lymphocytes are produced in the bone marrow and then go through a process of maturation in which they “learn” to distinguish self from non-self. B cells mature in the bone marrow, and T cells mature in the thymus. Both the bone marrow and thymus are considered primary lymphatic organs.
- Secondary lymphatic organs include the tonsils, spleen, and lymph nodes. There are four pairs of tonsils that encircle the throat. The spleen filters blood as well as lymph. There are hundreds of lymph nodes located in clusters along the lymphatic vessels. All of these secondary organs filter lymph and store lymphocytes, so they are sites where pathogens encounter and activate lymphocytes and initiate adaptive immune responses.
- Unlike the adaptive immune system, the innate immune system does not confer immunity. The innate immune system includes surface barriers, inflammation, the complement system, and a variety of cellular responses.
- The body’s first line of defense consists of three different types of barriers that keep most pathogens out of body tissues. The types of barriers are mechanical, chemical, and biological barriers.
- Mechanical barriers — which include the skin, mucous membranes, and fluids such as tears and urine — physically block pathogens from entering the body.
- Chemical barriers — such as enzymes in sweat, saliva, and semen — kill pathogens on body surfaces.
- Biological barriers are harmless bacteria that use up food and space so pathogenic bacteria cannot colonize the body.
- If pathogens breach the protective barriers, inflammation occurs. This creates a physical barrier against the spread of infection and repairs tissue damage. Inflammation is triggered by chemicals such as cytokines and histamines, and it causes swelling, redness, and warmth.
- The complement system is a complex biochemical mechanism that helps antibodies kill pathogens. Once activated, the complement system consists of more than two dozen proteins that lead to disruption of the cell membrane of pathogens and bursting of the cells.
- Cellular responses of the innate immune system involve various types of leukocytes (white blood cells). For example, neutrophils, macrophages, and dendritic cells phagocytize pathogens. Basophils and mast cells release chemicals that trigger inflammation. Natural killer cells destroy cancerous or virus-infected cells, and eosinophils kill parasites.
- Many pathogens have evolved mechanisms that help them evade the innate immune system. For example, some pathogens form a protective capsule around themselves, and some mimic host cells so the immune system does not recognize them as foreign.
- The main cells of the adaptive immune system are lymphocytes. There are two major types of lymphocytes: T cells and B cells. Both types must be activated by foreign antigens to become functioning immune cells.
- Most activated T cells become either killer T cells or helper T cells. Killer T cells destroy cells that are infected with pathogens or are cancerous. Helper T cells manage immune responses by releasing cytokines that control other types of leukocytes.
- Activated B cells form plasma cells that secrete antibodies, which bind to specific antigens on pathogens or infected cells. The antibody-antigen complexes generally lead to the destruction of the cells, for example, by attracting phagocytes or triggering the complement system.
- After an adaptive immune response occurs, long-lasting memory B cells and memory T cells may remain to confer immunity to the specific pathogen that caused the adaptive immune response. These memory cells are ready to activate an immediate response if they are exposed to the same antigen again in the future.
- Immunity may be active or passive. Active immunity occurs when the immune system has been presented with antigens that elicit an adaptive immune response. This may occur naturally as the result of an infection or artificially as the result of immunization. Active immunity may last for years or even for life.
- Passive immunity occurs without an adaptive immune response by the transfer of antibodies or activated T cells. This may occur naturally between a mother and her fetus or her nursing infant, or it may occur artificially by injection. Passive immunity lasts only as long as the antibodies or activated T cells remain alive in the body, generally just weeks or months.
- Many pathogens have evolved mechanisms to evade the adaptive immune system. For example, human immunodeficiency virus (HIV) evades the adaptive immune system by frequently changing its antigens and by forming its outer envelope from the host’s cell membrane.
- An allergy is a disorder in which the immune system makes an inflammatory response to a harmless antigen. Any antigen that causes allergies is called an allergen. Common allergens include pollen, dust mites, mold, specific foods such as peanuts, insect stings, and certain medications such as aspirin.
- The prevalence of allergies has been increasing for decades, especially in developed countries where they are much more common than in developing countries. The hygiene hypothesis posits that this has occurred because humans evolved to cope with more pathogens than we now typically face in our relatively sterile environments in developed countries. As a result, the immune system “keeps busy” by attacking harmless antigens.
- Allergies occur when B cells are first activated to produce large amounts of antibodies to an otherwise harmless allergen and the antibodies attach to mast cells. On subsequent exposures to the allergen, the mast cells immediately release cytokines and histamines that cause inflammation.
- Mild allergy symptoms are frequently treated with antihistamines that counter histamines and reduce allergy symptoms. A severe systemic allergic reaction, called anaphylaxis, is a medical emergency that is usually treated with injections of epinephrine. Immunotherapy for allergies involves injecting increasing amounts of allergens to desensitize the immune system to them.
- Autoimmune diseases occur when the immune system fails to recognize the body’s own molecules as self and attacks them, causing damage to tissues and organs. A family history of autoimmunity and female gender are risk factors for autoimmune diseases.
- In some autoimmune diseases, such as type I diabetes, the immune system attacks, and damages specific body cells. In other autoimmune diseases, such as systemic lupus erythematosus, many different tissues and organs may be attacked and injured. Autoimmune diseases generally cannot be cured, but their symptoms can often be managed with drugs or other treatments.
- Immunodeficiency occurs when the immune system is not working properly, generally because one or more of its components are inactive. As a result, the immune system is unable to fight off pathogens or cancers that a normal immune system would be able to resist.
- Primarily immunodeficiency is present at birth and caused by rare genetic diseases. An example is severe combined immunodeficiency. Secondary immunodeficiency occurs because of some event or exposure experienced after birth. Possible causes include substance abuse, obesity, and malnutrition, among others.
- The most common cause of immunodeficiency in the world today is the human immunodeficiency virus (HIV), which infects and destroys helper T cells. HIV is transmitted through mucous membranes or body fluids. The virus may eventually lead to such low levels of helper T cells that opportunistic infections occur. When this happens, the patient is diagnosed with acquired immunodeficiency syndrome (AIDS). Medications can control the multiplication of HIV in the human body but not eliminate the virus completely.
Up to this point, this book has covered body systems that carry out processes within individuals, such as the digestive, muscular, and immune systems. Read the next chapter to learn about the body system that allows humans to produce new individuals — the reproductive system.
Chapter Summary Review
1. The skin plays a role in establishing mechanical, chemical, and biological barriers that protect the body against pathogens. Give one example of how the skin contributes to each type of barrier.
2. Compare and contrast a pathogen and an allergen.
3. Describe three ways in which pathogens can enter the body.
4. For each of the following immune responses, state whether it is an innate or adaptive immune response.
b. Lymphocyte activation
c. Phagocytosis by leukocytes
d. Plasma cell maturation
5. The complement system involves the activation of several proteins to kill pathogens. Why do you think this is considered part of the innate immune system instead of the adaptive immune system?
6. Why are innate immune responses generally faster than adaptive immune responses?
7. True or False. There is more than one type of immune system cell that can carry out phagocytosis.
8. True or False. Semen can act as a chemical barrier against pathogens.
9. True or False. Leukocytes in the innate immune system are all phagocytic.
10. Which type of immunity is triggered by vaccination?
A. Artificially acquired active immunity
B. Artificially acquired natural immunity
C. Artificially acquired passive immunity
D. Innate immunity
11. Explain how an autoimmune disease could be triggered by a pathogen.
12. a. What is an opportunistic infection?
b. Name two diseases or conditions that could result in opportunistic infections. Explain your answer.
13. Match each description below with the cell type that best fits it from the list provided. Each cell type is used only once.
Cell types: mast cells; B cells; killer T cells
A. Directly destroys body cells that are cancerous or infected with a pathogen
B. Secretes histamines and are involved in allergies
C. Once activated, these cells multiply and their daughter cells mature into plasma cells
14. Which cell type in the immune system can be considered an “antibody factory”?
15. Besides foreign pathogens, what is one other thing that the immune system protects the body against?
16. What cell type in the immune system is infected and killed by HIV?
17. What is the difference between primary lymphoid organs and secondary lymphoid organs? Give one example of each in your answer.
18. a. Name two types of cells that produce cytokines in the immune system.
b. What are two functions of cytokines in the immune system?
19. Many pathogens evade the immune system by altering their outer surface in some way. Based on what you know about the functioning of the immune system, why is this often a successful approach?
20. Major histocompatibility complex proteins:
A. are involved in antigen-presentation by B cells
B. help distinguish cells as self
C. produce histamines
D. A and B
21. What is “missing self” and how does this condition arise?
22. True or False. Sometimes only part of a pathogen is used to create a vaccine.
23. True or False. An antigen is the same thing as an allergen.